The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Zhang, Yonghua

doi:10.4172/2157-2518.s2-001

Cited by 9 publications

(14 citation statements)

References 136 publications

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“…Also, increased expression of progranulin has been associated with tumor progression and invasiveness in several cancers, including ovarian cancer (Devoogdt et al, 2009;Cuevas-Antonio et al, 2010), renal carcinoma (Donald et al, 2001), hepatocellular carcinoma (Ho et al, 2008), myeloma (Wang et al, 2006), prostate cancer (Monami et al, 2009), endometrial cancer (Jones et al, 2006), breast cancer (Li-qin et al, 2011) and lung cancer (Stewart, 2010;Hu et al, 2006) based on a variety of experimental approaches. So, this diversity of anatomical sites, including cancer bladder detected in this study, is suggestive of a significant role for progranulin in tumor biology (Zhang and Bateman, 2011).…”

Section: Discussionsupporting

confidence: 58%

“…It also acts as a cell survival factor and as a promoter of invasion for a variety of cancer cells. It is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as myelomas and glioblastomas (Zhang and Bateman, 2011). Monami et al (2006), used recombinant progranulin on 5637 transitional cell carcinoma-derived cells to provide the first evidence for the role of progranulin in promoting migration and invasion of bladder cancer cells and to support the hypothesis that this growth factor may play a significant role in the establishment of the transformed phenotype in bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

“…The growth factor progranulin (also known as proepithelin, acrogranin, PC-derived growth factor, or granulin-epithelin precursor) is a secreted glycoprotein (Zhang and Bateman, 2011) that was originally isolated from different sources by several independent laboratories (Plowman et al, 1992;Baba et al, 1993;Xu et al, 1998). It is translated as a 593 amino acid protein with a predicted molecular weight of ~68 kDa, but due to its high degree of glycosylation, it is typically secreted as a ~90 kDa protein Science Publications AJBB (Monami et al, 2006;Zhu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Role of Progranulin Gene Expression as a Molecular Biomarker for Bladder Cancer

Anas¹

2012

American Journal of Biochemistry and Biotechnology

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Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumor and estimation of risk of future progression has a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumor, their accuracy is not ideal. Progranulin is a growth factor that may play a critical role in bladder cancer. Previous reports have shown that progranulin is essential for cellular proliferation. In this study, we examined whether progranulin gene expression can be a novel molecular marker for bladder cancer and evaluated its potential suitability as a urinary biomarker for bladder cancer diagnosis. Expression of progranulin gene in tissue and urine sediment of normal and bladder cancer samples was performed by semi-quantitative reverse transcription-PCR. Also, progranulin level was estimated in 90 voided urine samples, including 65 bladder cancer patients and 25 healthy volunteers using the quantitative enzyme immunoassay technique. Significant over-expression of progranulin was observed in bladder cancer cases. This over-expression was correlated with the stage and grade of the cancer. The urinary progranulin level was significantly higher in bladder cancer patients compared to control subjects (means: 18.39±0.56 and 9.17±0.41 ng mL −1 , respectively; p<0.001). Furthermore, the urinary progranulin level at cut off value = 11.275 has a sensitivity = 93.8% and a specificity = 84% for cancer bladder diagnosis. Urinary progranulin may be considered as a simple, noninvasive test with acceptable sensitivity and specificity for bladder cancer diagnosis and may greatly improve the current diagnosis based on cytology. However, this is a preliminary study that opens the window for further researches to fully validate its results in progranulin and cancer bladder research.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Progranulin Gene Expression as a Molecular Biomarker for Bladder Cancer

Anas¹

2012

American Journal of Biochemistry and Biotechnology

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“…PGRN is a 68 kDa, glycosylated protein that is ubiquitously expressed in many cells and has pleiotropic roles in physiology such as neuronal growth, differentiation and survival [2][3][4] , wound healing and repair [5][6] , and immunomodulation 7 . The protein is also known to play a roles in tumor growth and metastasis by its growth-promoting and angiogenic characteristics 8 . PGRN is also linked to neurodegenerative disorders with the haploinsufficiency of the protein being implicated in frontotemporal dementia (FTD) 9 while a complete loss of PGRN leads to neuronal ceroid lipofuscinosis, a lysosomal storage disease 10 .…”

Section: Introductionmentioning

confidence: 99%

Are Granulins Copper Sequestering Proteins?

Bhopatkar

Rangachari

2020

Preprint

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Granulins (GRN 1-7) are short (∼6 kDa), cysteine-rich proteins that are generated upon the proteolytic processing of progranulin (PGRN). These modules, along with their precursor, have been implicated in multiple pathophysiological roles, especially in neurodegenerative diseases. Our previous investigations into GRN-3 and GRN-5 reveal them to be fully disordered in the reduced form and implicate redox sensitive attributes to the proteins. Such redox-dependent modulation has become associated with proteins involved in oxidative stress regulation and maintaining metal-homeostasis within cells. To probe whether GRNs play a contributory role in such functions, we tested the metal binding potential of the reduced form of GRNs -3 and -5 under neutral and acidic pH mimicking cytosolic and lysosomal conditions, respectively. We found, at neutral pH, both GRNs selectively bind Cu(II) and no other divalent cations. Binding of Cu(II) also partly triggered the oxidative multimerization of GRNs via uncoordinated cystines at both pH conditions. Furthermore, binding did not induce gain in secondary structure and the protein remained disordered. Overall, the results indicate that GRN-3 and -5 have a surprisingly strong affinity for Cu(II) in the pM range, comparable to known copper sequestering proteins. This data also hints at a potential of GRNs to reduce Cu(II) to Cu(I), a process that has significance in mitigating Cu-induced ROS cytotoxicity in cells. Together, this report uncovers a metal-coordinating capability of GRNs for the first time, which could have profound significance in their structure and function.

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“…It has growth factor-like properties, stimulating cell proliferation, motility, and survival. It promotes tumorigenesis in vivo, is overexpressed in many cancers, and, as with EphA2, its expression often correlates with more invasive tumors and poor patient outcomes (Zhang and Bateman, 2011). It is angiogenic.…”

mentioning

confidence: 99%